| Crystallographic studies of chemically modified nucleic acids: a backward glance. | |
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MedLine Citation:
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PMID: 20087997 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Chemically modified nucleic acids (CNAs) are widely explored as antisense oligonucleotide or small interfering RNA (siRNA) candidates for therapeutic applications. CNAs are also of interest in diagnostics, high-throughput genomics and target validation, nanotechnology and as model systems in investigations directed at a better understanding of the etiology of nucleic acid structure, as well as the physicochemical and pairing properties of DNA and RNA, and for probing protein-nucleic acid interactions. In this article, we review research conducted in our laboratory over the past two decades with a focus on crystal-structure analyses of CNAs and artificial pairing systems. We highlight key insights into issues ranging from conformational distortions as a consequence of modification to the modulation of pairing strength, and RNA affinity by stereoelectronic effects and hydration. Although crystal structures have only been determined for a subset of the large number of modifications that were synthesized and analyzed in the oligonucleotide context to date, they have yielded guiding principles for the design of new analogs with tailor-made properties, including pairing specificity, nuclease resistance, and cellular uptake. And, perhaps less obviously, crystallographic studies of CNAs and synthetic pairing systems have shed light on fundamental aspects of DNA and RNA structure and function that would not have been disclosed by investigations solely focused on the natural nucleic acids. |
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Authors:
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Martin Egli; Pradeep S Pallan |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Review |
Journal Detail:
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Title: Chemistry & biodiversity Volume: 7 ISSN: 1612-1880 ISO Abbreviation: Chem. Biodivers. Publication Date: 2010 Jan |
Date Detail:
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Created Date: 2010-01-26 Completed Date: 2010-04-08 Revised Date: 2011-02-16 |
Medline Journal Info:
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Nlm Unique ID: 101197449 Medline TA: Chem Biodivers Country: Switzerland |
Other Details:
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Languages: eng Pagination: 60-89 Citation Subset: IM |
Affiliation:
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Department of Biochemistry, School of Medicine, Vanderbilt University, Nashville, Tennessee 37232-0146, USA. martin.egli@vanderbilt.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Base Pairing Bicyclo Compounds / chemistry Carbohydrates / chemistry Crystallography, X-Ray Molecular Conformation Nucleic Acids / chemistry* Nucleotides / chemistry Sulfhydryl Compounds / chemistry |
| Grant Support | |
ID/Acronym/Agency:
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R01 GM055237-14/GM/NIGMS NIH HHS; R01 GM55237/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Bicyclo Compounds; 0/Carbohydrates; 0/Nucleic Acids; 0/Nucleotides; 0/Sulfhydryl Compounds |
| Comments/Corrections | |
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